Ion traps have been employed for a number of different applications in which control over the motions of ions is desired. In particular, ion traps have been utilized as mass analyzers or sorters in mass spectrometry (MS) systems. The ion trap of an ion trap-based mass analyzer may be formed by electric and/or magnetic fields. The present disclosure is primarily directed to ion traps formed solely by electric fields without magnetic fields.
Insofar as the present disclosure is concerned, MS systems are generally known and need not be described in detail. Briefly, a typical MS system includes a sample inlet system, an ion source, a mass analyzer, an ion detector, a signal processor, and readout/display means. Additionally, the modern MS system includes a computer for controlling the functions of one or more components of the MS system, storing information produced by the MS system, providing libraries of molecular data useful for analysis, and the like. The MS system also includes a vacuum system to enclose the mass analyzer in a controlled, evacuated environment. Depending on design, all or part of the sample inlet system, ion source and ion detector may also be enclosed in the evacuated environment.
In operation, the sample inlet system introduces a small amount of sample material to the ion source, which may be integrated with the sample inlet system depending on design. The ion source converts components of the sample material into a gaseous stream of positive or negative ions. The ions are then accelerated into the mass analyzer. The mass analyzer separates the ions according to their respective mass-to-charge ratios. The term “mass-to-charge” is often expressed as m/z or m/e, or simply “mass” given that the charge z or e often has a value of 1. Many mass analyzers are capable of distinguishing between very minute differences in m/z ratio among the ions being analyzed. The mass analyzer produces a flux of ions resolved according to m/z ratio that is collected at the ion detector. The ion detector functions as a transducer, converting the mass-discriminated ionic information into electrical signals suitable for processing/conditioning by the signal processor, storage in memory, and presentation by the readout/display means. A typical output of the readout/display means is a mass spectrum, such as a series of peaks indicative of the relative abundances of ions at detected m/z values, from which a trained analyst can obtain information regarding the sample material processed by the MS system.
Referring to FIG. 1, most conventional ion traps are produced by a three-dimensional electric field using a three-dimensional ion trap electrode assembly 10. This type of electrode structure was disclosed as early as 1960 in U.S. Pat. No. 2,939,952 to Paul et al. As indicated by the arrow in FIG. 1, this electrode assembly 10 is rotationally symmetrical about the z-axis. The electrode assembly 10 is constructed from a top electrode or end cap 12, a bottom electrode or end cap 14, and a center electrode or ring 16, which are formed by hyperboloids of revolution. Top and bottom electrodes 12 and 14 can include respective apertures 12A and 14A, one serving as an entrance aperture for conducting ions into the trap and the other serving as an exit aperture for ejecting ions from the trap, or both serving as exit apertures. As an alternative to using an external ionization device and injecting ions into the electrode assembly 10, ionization can be carried out within the electrode structure by any known means such as directing an electron beam through one of apertures 12A or 14A into the interior of electrode assembly 10.
An alternating (AC) voltage, which generally must have an RF frequency, is typically applied to ring 16 to create a potential difference between ring 16 and end caps 12 and 14. This AC potential forms a three-dimensional quadrupolar trapping field that imparts a three-dimensional restoring force directed towards the center of electrode assembly 10. The AC voltage is adjustable, and thus the trapping field is electrodynamic and well-suited for mass scanning operations. Ions are confined within an electrodynamic quadrupole field when their trajectories are bounded in both the r and z directions. The ion motion in the trapping field is nearly periodic. In a pure quadrupole trapping field, the ion motions in both the r and z directions are independent of each other. Accordingly, the equations of motion for a single ion in the trapping field can be resolved into a pure r motion and a pure z motion that have identical mathematical forms described by the well known Mathieu equation, which can be expressed in various forms. See, e.g., March et al., Quadrupole Storage Mass Spectrometry, Wiley, New York (1991).
The Mathieu equation for the axial motion depends on two parameters az and qz, often termed trapping, scanning, or Mathieu parameters, which characterize the solutions in the z-axis direction. Similar parameters, ar and qr exist for the r-axis motions. These parameters define a two-dimensional region in (au, qu) space for the coordinate u (r or z) in which the ion motions are bounded and therefore stable. An ion lying outside of a stability region is unstable, in which case the displacement of the ion grows without bounds and the ion is ejected from the trapping field; that is, the parameters of the trapping field for this particular ion are such that the ion cannot be trapped. A graphical representation or mapping of (au, qu) space for radial and axial stable and unstable ion motion is known as a stability diagram. A point in (au, qu) space defines the operating point for an ion. The parameters au and qu depend on the m/z ratio of the ion, the spacing of the electrode structure relative to the center of the internal volume it defines, and the frequency of the AC trapping potential. In addition, the parameter au depends on the amplitude of the DC component (if present) of the trapping field, and the parameter qu depends on the amplitude of the AC component. Therefore, for a given electrode arrangement the magnitude and frequency of the AC trapping potential can be set so that only ions of a desired m/z range of interest are stable and thus trappable. For small values of au, and qu, the pseudo-harmonic motion of an ion can be characterized by the dominant fundamental frequency for motion in the u coordinate, simplifying mathematical treatment of the ion motion.
Various techniques have been utilized for increasing ion oscillations and ejecting ions from a three-dimensional ion trap such as illustrated in FIG. 1, usually for the purpose of detecting the ions as part of a mass spectrometry experiment. A three-dimensional quadrupole ion trap was employed to distinguish ions of different mass-to-charge ratios formed by photo-dissociation inside of the trap, as reported by K. B. Jefferts, Physical Review Letters, 20 (1968) 39. The trapping field frequency was swept and ions of successive mass-to-charge ratios were made unstable in the axial direction and were sequentially ejected from the trap and detected by an electron multiplier. U.S. Pat. No. 4,540,884 to Stafford et al. discloses a similar technique of mass-selective instability scanning. In this patent, ions of an m/z range of interest are trapped in a quadrupole field. The amplitude of the RF voltage is then increased such that ions of increasing m/z values become unstable. Unstable ions are ejected from the trapping field and detected to provide a mass spectrum. Disadvantages of the mass-selective instability scanning technique have been noted, for example, in U.S. Pat. No. 4,882,484 to Franzen et al. First, the direction of ion ejection cannot be adequately controlled or focused. If a perforation is provided in an electrode of three-dimensional trap structure 10 to pass ejected ions to a detector, only a small percentage of ions ejected by mass-selective instability will actually be directed through the perforation. Second, the nature of the quadrupole trapping field is such that the field strength is zero at the center. Hence, ions at or near the center of the field cannot be ejected unless some additional influence is introduced into the system.
In another technique, the amplitude of the ion motion in the radial or axial direction can be increased by the application of a supplemental AC field having a frequency and symmetry that is in resonance with one of the frequencies of the ion motion. If the amplitude of the ion motion is increased enough, the ion will be driven to the surface of an electrode. If a hole exists in the electrode where the ion is directed, such as aperture 12A or 14A in FIG. 1, the ion will escape the trapping field altogether and exit the trap. Dipolar resonant excitation was used to eject ions from the three-dimensional trap to an external detector by applying an axial resonant field to end caps 12 and 14, as reported by Ensberg et al., The Astrophysical Journal, 195 (1975) L89. The frequency of the applied field was swept and ions of successive mass-to-charge ratios were ejected from the trap. A variant of these methods is used in commercial ion trap mass spectrometers to eject ions by dipolar resonant excitation. The amplitude of the RF trapping field is increased linearly to increase the operating point (qz, az) of the ions until the fundamental frequency of ion motion comes into resonance with a supplementary AC voltage on end caps 12 and 14 and resonant ejection occurs. It has also been demonstrated that dipolar resonant excitation can be effected to eject unwanted ions from a three-dimensional quadrupole ion trap formed from hyperboloids of revolution having two sheets. See Fulford et al., Int. J. Mass Spectrom. Ion Phys., 26 (1978) 155; and Fulford et al., J. Vac. Sci. Technology, 17 (1980) 829. In these studies, a supplementary AC voltage was applied to end caps 12 and 14 of the ion trap, out of phase, to produce an AC dipole field in the axial direction. As noted, resonant ejection occurs only for those ions having an axial frequency of motion (or secular frequency) equal to the frequency of the supplementary AC field. The ions in resonance with the supplementary field increase the amplitude of their axial oscillation until the kinetic energy of the ions exceeds the restoring force of the RF trapping field and ion ejection occurs in the axial direction. Ejection using a supplemental AC dipole was extended to the tandem (MS/MS) mode of mass spectrometry in U.S. Pat. No. 4,736,101 to Syka et al.
U.S. Pat. No. 4,882,484 to Franzen et al discloses a mass-selective resonance ejection technique that addresses the zero-field strength problem attending quadrupole trapping fields. An RF excitation potential is applied across end caps 12 and 14. If the z-direction secular frequency of an ion matches the frequency of the excitation voltage, the ion absorbs energy from the excitation field and the amplitude of ion motion in z-direction increases until the ion is ejected to one of end caps 12 or 14. This technique can be used to eject ions of consecutive m/z values by either scanning the excitation frequency while holding the quadrupole trapping field constant or scanning the amplitude of the trapping field while holding the excitation frequency constant. Franzen et al further proposed to provide a mechanically or geometrically “non-ideal” ion trap structure to deliberately introduce field faults that result in a nonlinear resonance condition. Specifically, ring 16 or end caps 12 and 14 are shaped to depart from the ideal hyperbolic curvature, thereby introducing an octopole component in the trapping field. In this manner, ion excursions can be compressed along the z-axis to enhance ejection to an aperture 12A or 14A aligned with the z-axis at the apex of an end cap 12 or 14. Nonetheless, this technique fails to eject all ions in a single desired direction. In addition, the mechanical solution can add to the cost, complexity, and precision of the manufacturing process. Moreover, the octopole field is mechanically fixed; its parameters cannot be changed.
Ion ejection by quadrupolar resonant excitation can be effected by the application of a supplementary AC voltage applied in phase to the end cap electrodes. Parametric resonant excitation by a supplemental quadrupole field causes ion amplitudes to increase in the axial direction if the ion frequency is one-half of the supplementary quadrupole frequency. Parametric resonant excitation has been investigated theoretically. See U.S. Pat. No. 3,065,640 to Langmuir et al.; and Alfred et al., Int. J. Mass Spectrom. Ion Processes., 125 (1993) 171. While a supplemental dipole field excites ions to oscillate with an amplitude that increases linearly with time, a supplemental quadrupole field causes an exponential increase in the amplitude of the oscillations. See U.S. Pat. No. 5,436,445 to Kelley et al. However, as in the case of the main quadrupole trapping field, the supplemental quadrupole field has a value of zero at the center of the ion trap. When a buffer gas such as helium is used to dampen the ion trajectories to the center of the trap, parametric excitation is ineffectual due to the vanishing strength of the supplemental quadrupole field. It is necessary to displace the ions from the center of the supplemental quadrupole field to a location where the field has a non-zero value in order to have a finite excitation force applied to the ions.
As described in U.S. Pat. No. 5,381,007 to Kelly, a weak resonant dipole field having a frequency of one-half of the parametric frequency can be used to displace ions from the center of the trap when the operating point of the ions is changed to bring the ion fundamental frequency into resonance with the dipole field. Because the parametric frequency is twice the dipole frequency, the ion will absorb power from the supplemental quadrupole field. This mode of ion ejection, in which power is absorbed sequentially from the dipole and then the quadrupole field, is adequate for ion ejection in a static trapping field where the fundamental frequency of the ion motion is not changing due to the amplitude of the RF field. This mode of ion ejection is not optimal, however, when the trapping field amplitude is changing as is normally the case for mass scanning. In this case, the RF trapping field amplitude is increased to increase the fundamental frequency of the ion motion, bringing it into resonance first with the dipole field. The dipole field displaces the ion from the center of the trap where the quadrupole field is zero. After the ion has been displaced from the center, it can then absorb power from the supplemental quadrupole field if it is in resonance with the parametric resonance. Therefore, it is necessary to fix the dipole resonant frequency at a value less than one-half of the parametric resonance so that as the fundamental frequency of the ion motion is increased by increasing the trapping field RF amplitude, the ion motion will sequentially be in resonance with the dipole field and then with the quadrupole field. See U.S. Pat. No. 5,468,957 to Franzen.
As previously noted, the geometry of the electrode structure of three-dimensional ion trap 10 can be modified to deliberately introduce a fourth-order octopole component into the trapping field to enhance mass resolution, as described for example by Franzen et al., Practical Aspects of Ion Trap Mass Spectrometry, CRC Press (1995). Higher-order fields can be obtained by increasing the separation between end caps 12 and 14 while maintaining ideal hyperbolic surfaces. See Louris et al., Proceedings of the 40th ASMS Conference on Mass Spectrometry and Allied Topics, (1992) 1003. These surfaces have asymptotes at 35.26° with respect to the symmetric radial plane of the ideal ion trap. Alternatively, the surfaces of end caps 12 and 14 can be shaped with an angle of 35.96° while maintaining the ideal separation between end caps 12 and 14. See, e.g., U.S. Pat. No. 4,975,577 to Franzen et al.; U.S. Pat. No. 5,028,777 to Franzen et al.; and U.S. Pat. No. 5,170,054 to Franzen. For either geometry the trapping field is symmetric with respect to the radial plane.
A disadvantage of the foregoing prior art techniques is that even if ion movement can be concentrated along a single axis to improve scanning the ions out from the trapping field, the ions are nevertheless equally likely to be ejected in either direction along the axis. Thus, only half of the ejected ions may actually reach a detector. This problem was addressed in U.S. Pat. No. 5,291,017 to Wang et al., assigned to the assignee of the present disclosure. Wang et al. teach that electrical circuitry means can be employed to apply an AC dipole and/or monopole voltage to end caps 12 and 14 at the same frequency as the quadrupole trapping voltage. This has the effect of creating an asymmetrical trapping field in which the center of the trapping field is displaced from the geometrical center of the three-dimensional electrode structure. The supplemental voltage distorts the symmetry of the quadrupole field at the center, such that positive and negative ions are separated and ions are preferentially ejected in the direction of a target end cap 12 or 14.
A new ion ejection method described in U.S. Pat. No. 5,714,755 to Wells et al., assigned to the assignee of the present disclosure, also utilizes a quadrupole trapping field that is asymmetric with respect to the radial plane. The asymmetric trapping field is generated by adding an AC voltage out of phase to each end cap 12 and 14 and at the same frequency as the RF voltage applied to ring 16. This trapping field dipole (TFD) component causes the center of the trapping field to be non-coincident with the geometric center of ion trap electrode assembly 10. The first order effect of adding the dipole component to the trapping field is to displace the ions toward the end cap 12 or 14 that has the TFD component in phase with the RF voltage applied to ring 16. A second order effect is to superimpose a substantial hexapole field on the trapping field. The resulting multipole trapping field has a nonlinear resonance at the operating point of βz=⅔ in the stability diagram pertaining to the ion trap structure. Since the ions are already displaced from the geometrical center of the trap by the asymmetric trapping field, the hexapole resonance has a finite value where the ions reside. Likewise at this operating point, a parametric resonance due to a supplementary quadrupole field will also have a non-zero value. Finally, the addition of a supplementary dipole field at this point will also cause dipolar resonant excitation. All three fields will have non-zero values at the operating point of βz=⅔, and therefore a triple resonance condition exists. An ion moved to this operating point will be in resonance with, and absorb power from, all three fields simultaneously.
At the operating point of the triple resonance, power absorption by the ions is nonlinear. The amplitude of the axial ion motion also increases nonlinearly with time and the ion is quickly ejected from the trap. Ion trajectories are less affected by collisions with the damping gas in the region of the resonance due to the short ejection time, and resolution is improved. Moreover, the displacement of the trapping center towards the exit end cap 12 or 14 causes the ions to be ejected exclusively through this electrode, thus doubling the number of ions detected. The system disclosed in U.S. Pat. No. 5,714,755 thus provides significant advantages in the operation of three-dimensional ion trap 10, particularly in the ability to establish an asymmetrical trapping field and nonlinear resonance by a controllable, adjustable electrical means. However, a three-dimensional trap structure 10 does not offer the advantages of a linear, two-dimensional trap structure as described below.
In addition to three-dimensional ion traps, linear and curvilinear ion traps have been developed in which the trapping field includes a two-dimensional quadrupolar component that constrains ion motion in the x-y (or r-θ) plane orthogonal to the elongated linear or curvilinear axis. A two-dimensional electrode structure can be conceptualized from FIG. 1 by replacing end caps 12 and 14 with top and bottom hyperbolically-shaped electrodes that are elongated in the direction into the drawing sheet, and replacing ring 16 with an opposing pair of side electrodes similar to the top and bottom electrodes that are elongated in the same direction and moved closer together. The result is a set of four axially elongated electrodes arranged in parallel about a central axis, with opposing pairs of electrodes electrically interconnected. The cross-section of this four-electrode structure is similar to the electrode set 110, 112, 114, 116 utilized in embodiments of the present disclosure as shown, for example, in FIG. 2A herein.
Ion guiding and trapping devices utilizing a two-dimensional geometry have been known in the art for many decades. The basic quadrupole mass filter constructed from four parallel rods of hyperbolic shape, or from cylindrical rods approximating the hyperbolic shape, was disclosed as early as the afore-mentioned U.S. Pat. No. 2,939,952 to Paul et al. A curved ion trap formed by bending a two dimensional RF quadrupole rod assembly into a circle or oval “racetrack” was described by Church, Journal of Applied Physics, 40, 3127 (1969). A linear two dimensional ion trap formed from a two dimensional RF quadrupole rod assembly was employed to study ion-molecule reactions, as reported by Dolnikowski et al., Int. J. Mass Spectrom. and Ion Proc., 82, 1 (1988).
In the case of a linear ion trap, ions are confined within an electrodynamic quadrupole field when their trajectories are bounded in both the x- and y-directions. The restoring force drives ions toward the central axis of the two-dimensional electrode structure. As in the case of three-dimensional ion trap 10, in a pure quadrupole trapping field of a linear ion trap, the ion motion in both the x- and y-directions are independent of each other and the ion motion in the trapping field is nearly periodic. The equations of motion for a single ion in the trapping field can be resolved into a pure x motion and a pure y motion that have identical mathematical forms described by the Mathieu equation. The Mathieu equation for the y-axis motion again depends on the two trapping parameters ay and qy characterizing the solutions in the y-axis direction. Similar parameters, ax and qy, exist for the x-axis motions. Trapped ions require that stability exist in both the x- and y-directions simultaneously. It is known that non-ideal hyperbolic electrodes, or electrodes of circular shape that are used to approximate hyperbolic fields, generate nonlinear resonances within the field. It is further known, however, that these nonlinear resonances degrade the performance of quadrupole mass filters. Prior to the present disclosure, it is has not been appreciated that nonlinear resonances can be useful in linear ion traps.
For many applications, a linear ion trap provides advantages over a three-dimensional ion trap such as shown in FIG. 1. For instance, the volume of the electrode structure available for ion storage in a linear ion trap can be increased by increasing the linear dimension of the electrode structure, i.e., its axial length. By comparison, the only practicable way to increase the storage volume in the three-dimensional ion trap 10 in FIG. 1 is to increase the radial distance of the hyperbolic electrode surfaces from the center point of the volume, which undesirably increases the RF voltages required for operation. In addition, as compared with three-dimensional ion trap 10, the linear ion trap geometry is better suited for the injection of ions from an external source, as may be preferable to carrying out ionization directly in the volume of the electrode structure. Ions can be injected from an axial end of the linear ion trap structure instead of between adjacent electrodes, and the axial motion of the ion can be stabilized by collisions with a damping gas and/or application of DC voltages at the axial ends of the linear trap structure. Such advantages have been recognized, for instance, in U.S. Pat. No. 4,755,670 to Syka et al. In U.S. Pat. No. 5,420,425 to Bier et al., it was further suggested that increasing the ion storage volume by radially increasing the electrode spacing is disadvantageous because it decreases the m/z range of ions trappable in the volume.
U.S. Pat. No. 4,755,670 to Syka et al. discloses a linear ion trap utilized as a mass spectrometer. In this patent, ion detection is performed by means of image currents induced in the trap electrodes from the characteristic oscillation of ions in the trap due to an applied supplemental AC voltage pulse. The mass spectrum is formed by the Fourier Transform of the time domain image currents to produce a frequency domain spectrum. As in the case of many three-dimensional ion traps, the operation of this linear ion trap is not capable of ejecting ions in a single direction and hence many trapped ions are lost when ejected and thus are not detected.
U.S. Pat. No. 5,420,425 to Bier et al. teaches the use of a two-dimensional RF quadrupole rod assembly as a linear ion trap mass spectrometer. The disclosed method for ion ejection is based on the mass-selective instability scanning technique disclosed in U.S. Pat. No. 4,540,884 to Stafford et al. or on the mass-selective resonance scanning technique disclosed in U.S. Pat. No. 4,736,101 to Syka et al. Ions are ejected from the trap in a transverse direction (i.e., radial relative to the center axis of the electrode assembly) by making the ions either unstable or resonantly excited, causing the ions to be ejected from the trapping volume through a slot in the electrodes and into an ion detector. As in all linear ion traps of the prior art, the center of the trapping field coincides with the structural center axis of the linear electrode structure, i.e., the trapping field is symmetrical. In addition, while the ions can be ejected along one axis, they cannot be ejected in a single direction. Thus, many ions are wasted in the sense that they cannot contribute to the measurements taken for producing a mass spectrum.
The use of a linear ion trap as a mass spectrometer was also reported in U.S. Pat. No. 6,177,668 to Hager, which teaches a linear ion trap in which ion detection occurs by means of axial mass-selective ion ejection. That is, ions are ejected from the linear ion trap along the axis of symmetry of the trap, rather than orthogonal to this axis, and into an ion detector. Ions are mass-selected for ejection by means of an auxiliary AC field formed by applying an AC potential at an exit lens, or an auxiliary AC resonant dipole field formed by applying an AC potential on a pair of opposing electrodes. When the ions are brought into resonance by increasing the RF trapping field amplitude, their amplitude of oscillation increases. The axial potential decreases as the distance from the axis is increased, thereby allowing ions that have increased transverse amplitudes of oscillation to escape the axial potential barrier.
Therefore, a need exists for a linear ion trap apparatus and method in which an asymmetrical trapping field can be formed. A need also exists for a linear ion trap apparatus and method in which ions can be preferentially ejected in a single direction. A need also exists for a linear ion trap apparatus and method in which the amplitude of ion motion can be increased over time at a rate faster than a linear rate. A need further exists for a linear ion trap apparatus and method in which ions can be ejected by nonlinear resonant excitation, and particularly in a single direction. A need further exists for a linear ion trap apparatus and method in which components added to the basic trapping field do not need to be switched on and off during operation of the apparatus.